DESCRIPTION (Applicant's Description): Richard E. Sutton, M.D., Ph.D. is committed to a career of academic medicine. His basic science training has covered many areas, and most recently he has been relearning molecular biology and attempting to identify the HTLV-1 cellular receptor. The K08 award will allow him to continue those efforts in a supervised, structured setting, while at the same time he can expand his molecular biology expertise, learn some protein and receptor-ligand biochemistry, and perform gene targeting in mice. In a few years, Dr. Sutton hopes to obtain a position in a division of Infectious Diseases at a major academic center, with an appointment in a basic science department. He would plan on spending 80 percent of his time at the bench, and 20 percent on in-patient and out-patient clinical services. The proposed work will be conducted in the Howard Hughes Medical Institute at the Beckman Center, a modern molecular biology facility at Stanford University. Most necessary equipment, supplies, and support services are located in Beckman. The facility provides a rich intellectual milieu, and scientific interactions are possible with other Medical School departments along with the rest of the campus. His sponsor, Dr. Pat Brown, has extensive training and experience in the field of retroviruses and molecular biology, with specific interests in novel methods of gene mapping, viral core-host protein interactions, and proviral integration enzymology. The cellular receptor of human T-cell leukemia virus-1 (HTLV-1) has yet to be identified. The objective of this proposal is to continue Dr. Sutton's efforts to clone the receptor by use of gene transfer and screening or selection using high titer HIV (HTLV-1) pseudovirions that he has generated. The receptor will then be characterized in terms of its tissue distribution and basic protein structure. Receptor structure and function will then be explored by site-directed mutagenesis, aided by raising rabbit antisera against the receptor. The biological role of the receptor will addressed by gene targeting in the mouse. It is hoped that cloning of the receptor will allow an understanding of HTLV-1 associated clinical disorders including leukemogenesis and will enhance the knowledge of viral pathogenesis and life cycle.